Titanium dioxide nanoparticles (TiO2 NPs) are used in a wide range of applications. Although inhalation of NPs is one of the most important toxicologically relevant routes, experimental studies on potential harmful effects of TiO2 NPs using a whole-body inhalation chamber model are rare. In this study, the profile of lymphocyte markers, functional immunoassays, and antioxidant defense markers were analyzed to evaluate the potential adverse effects of seven-week inhalation exposure to two different concentrations of TiO2 NPs (0.00167 and 0.1308 mg TiO2/m3) in mice. A dose-dependent effect of TiO2 NPs on innate immunity was evident in the form of stimulated phagocytic activity of monocytes in low-dose mice and suppressed secretory function of monocytes (IL-18) in high-dose animals. The effect of TiO2 NPs on adaptive immunity, manifested in the spleen by a decrease in the percentage of T-cells, a reduction in T-helper cells, and a dose-dependent decrease in lymphocyte cytokine production, may indicate immunosuppression in exposed mice. The dose-dependent increase in GSH concentration and GSH/GSSG ratio in whole blood demonstrated stimulated antioxidant defense against oxidative stress induced by TiO2 NP exposure.

• Keywords
• antioxidant defense, cytokines, immune response, immunotoxicity, inflammation, lymphocytes, nanoparticle inhalation, phagocytic activity and respiratory burst, titanium dioxide nanoparticles,
• Publication type
• Journal Article MeSH

BACKGROUND: Inhalation of lead oxide nanoparticles (PbO NPs), which are emitted to the environment by high-temperature technological processes, heavily impairs target organs. These nanoparticles pass through the lung barrier and are distributed via the blood into secondary target organs, where they cause numerous pathological alterations. Here, we studied in detail, macrophages as specialized cells involved in the innate and adaptive immune response in selected target organs to unravel their potential involvement in reaction to subchronic PbO NP inhalation. In this context, we also tackled possible alterations in lipid uptake in the lungs and liver, which is usually associated with foam macrophage formation. RESULTS: The histopathological analysis of PbO NP exposed lung revealed serious chronic inflammation of lung tissues. The number of total and foam macrophages was significantly increased in lung, and they contained numerous cholesterol crystals. PbO NP inhalation induced changes in expression of phospholipases C (PLC) as enzymes linked to macrophage-mediated inflammation in lungs. In the liver, the subchronic inhalation of PbO NPs caused predominantly hyperemia, microsteatosis or remodeling of the liver parenchyma, and the number of liver macrophages also significantly was increased. The gene and protein expression of a cholesterol transporter CD36, which is associated with lipid metabolism, was altered in the liver. The amount of selected cholesteryl esters (CE 16:0, CE 18:1, CE 20:4, CE 22:6) in liver tissue was decreased after subchronic PbO NP inhalation, while total and free cholesterol in liver tissue was slightly increased. Gene and protein expression of phospholipase PLCβ1 and receptor CD36 in human hepatocytes were affected also in in vitro experiments after acute PbO NP exposure. No microscopic or serious functional kidney alterations were detected after subchronic PbO NP exposure and CD68 positive cells were present in the physiological mode in its interstitial tissues. CONCLUSION: Our study revealed the association of increased cholesterol and lipid storage in targeted tissues with the alteration of scavenger receptors and phospholipases C after subchronic inhalation of PbO NPs and yet uncovered processes, which can contribute to steatosis in liver after metal nanoparticles exposure.

• Keywords
• Cholesterol metabolism, Inhalation, Lead oxide nanoparticles, Liver macrophages, Lung macrophages,
• MeSH
• Cholesterol MeSH
• Type C Phospholipases * MeSH
• Metal Nanoparticles * chemistry   MeSH
• Humans MeSH
• Macrophages MeSH
• Lead MeSH
• Oxides MeSH
• Inflammation MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Cholesterol MeSH
• Type C Phospholipases * MeSH
• lead oxide MeSH Browser
• Lead MeSH
• Oxides MeSH

Copper oxide nanoparticles (CuO NPs) are increasingly used in various industry sectors. Moreover, medical application of CuO NPs as antimicrobials also contributes to human exposure. Their toxicity, including toxicity to the immune system and blood, raises concerns, while information on their immunotoxicity is still very limited. The aim of our work was to evaluate the effects of CuO NPs (number concentration 1.40×106 particles/cm3, geometric mean diameter 20.4 nm) on immune/inflammatory response and antioxidant defense in mice exposed to 32.5 µg CuO/m3 continuously for 6 weeks. After six weeks of CuO NP inhalation, the content of copper in lungs and liver was significantly increased, while in kidneys, spleen, brain, and blood it was similar in exposed and control mice. Inhalation of CuO NPs caused a significant increase in proliferative response of T-lymphocytes after mitogenic stimulation and basal proliferative activity of splenocytes. CuO NPs significantly induced the production of IL-12p70, Th1-cytokine IFN-γ and Th2-cytokines IL-4, IL-5. Levels of TNF-α and IL-6 remained unchanged. Immune assays showed significantly suppressed phagocytic activity of granulocytes and slightly decreased respiratory burst. No significant differences in phagocytosis of monocytes were recorded. The percentage of CD3+, CD3+CD4+, CD3+CD8+, and CD3-CD19+ cell subsets in spleen, thymus, and lymph nodes did not differ between exposed and control animals. No changes in hematological parameters were found between the CuO NP exposed and control groups. The overall antioxidant protection status of the organism was expressed by evaluation of GSH and GSSG concentrations in blood samples. The experimental group exposed to CuO NPs showed a significant decrease in GSH concentration in comparison to the control group. In summary, our results indicate that sub-chronic inhalation of CuO NPs can cause undesired modulation of the immune response. Stimulation of adaptive immunity was indicated by activation of proliferation and secretion functions of lymphocytes. CuO NPs elicited pro-activation state of Th1 and Th2 lymphocytes in exposed mice. Innate immunity was affected by impaired phagocytic activity of granulocytes. Reduced glutathione was significantly decreased in mice exposed to CuO NPs.

• Keywords
• antioxidant defense, copper oxide nanoparticles, cytokines, immune response, immunotoxicity, inflammation, lymphocytes, phagocytic activity and respiratory burst,
• MeSH
• Adaptive Immunity MeSH
• Antioxidants MeSH
• Cytokines MeSH
• Copper * toxicity   MeSH
• Mice MeSH
• Nanoparticles * toxicity   MeSH
• Oxides MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antioxidants MeSH
• Cytokines MeSH
• Copper * MeSH
• Oxides MeSH

The inhalation of metal (including lead) nanoparticles poses a real health issue to people and animals living in polluted and/or industrial areas. In this study, we exposed mice to lead(II) nitrate nanoparticles [Pb(NO3)2 NPs], which represent a highly soluble form of lead, by inhalation. We aimed to uncover the effects of their exposure on individual target organs and to reveal potential variability in the lead clearance. We examined (i) lead biodistribution in target organs using laser ablation and inductively coupled plasma mass spectrometry (LA-ICP-MS) and atomic absorption spectrometry (AAS), (ii) lead effect on histopathological changes and immune cells response in secondary target organs and (iii) the clearance ability of target organs. In the lungs and liver, Pb(NO3)2 NP inhalation induced serious structural changes and their damage was present even after a 5-week clearance period despite the lead having been almost completely eliminated from the tissues. The numbers of macrophages significantly decreased after 11-week Pb(NO3)2 NP inhalation; conversely, abundance of alpha-smooth muscle actin (α-SMA)-positive cells, which are responsible for augmented collagen production, increased in both tissues. Moreover, the expression of nuclear factor κB (NF-κB) and selected cytokines, such as tumor necrosis factor alpha (TNFα), transforming growth factor beta 1 (TGFβ1), interleukin 6(IL-6), IL-1α and IL-1β , displayed a tissue-specific response to lead exposure. In summary, diminished inflammatory response in tissues after Pb(NO3)2 NPs inhalation was associated with prolonged negative effect of lead on tissues, as demonstrated by sustained pathological changes in target organs, even after long clearance period.

• Keywords
• LA-ICP-MS imaging, clearance, inhalation, lead nanoparticles, toxicity,
• MeSH
• Actins agonists   genetics   immunology   MeSH
• Macrophages, Alveolar drug effects   immunology   pathology   MeSH
• Administration, Inhalation MeSH
• Biological Availability MeSH
• Nitrates pharmacokinetics   toxicity   MeSH
• Gene Expression MeSH
• Inhalation Exposure analysis   MeSH
• Interleukin-1alpha agonists   genetics   immunology   MeSH
• Interleukin-1beta agonists   genetics   immunology   MeSH
• Interleukin-6 agonists   genetics   immunology   MeSH
• Liver drug effects   immunology   pathology   MeSH
• Metal Nanoparticles administration & dosage   toxicity   MeSH
• Air Pollutants pharmacokinetics   toxicity   MeSH
• Mice, Inbred ICR MeSH
• Mice MeSH
• NF-kappa B agonists   genetics   immunology   MeSH
• Lead pharmacokinetics   toxicity   MeSH
• Lung drug effects   immunology   pathology   MeSH
• Half-Life MeSH
• Spectrophotometry, Atomic MeSH
• Tissue Distribution MeSH
• Tumor Necrosis Factor-alpha agonists   genetics   immunology   MeSH
• Transforming Growth Factor beta1 agonists   genetics   immunology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Actins MeSH
• alpha-smooth muscle actin, mouse MeSH Browser
• Nitrates MeSH
• Il1a protein, mouse MeSH Browser
• IL1B protein, mouse MeSH Browser
• Interleukin-1alpha MeSH
• Interleukin-1beta MeSH
• interleukin-6, mouse MeSH Browser
• Interleukin-6 MeSH
• Air Pollutants MeSH
• lead nitrate MeSH Browser
• NF-kappa B MeSH
• Lead MeSH
• Tgfb1 protein, mouse MeSH Browser
• Tumor Necrosis Factor-alpha MeSH
• Transforming Growth Factor beta1 MeSH